Ambient mass spectroscopy is a recent advancement in the field of analytical chemistry and has allowed for the analysis of samples with little-to-no sample preparation. Based on this concept, a variety of ambient ionization methods have been introduced, including desorption electrospray ionization (DESI), direct analysis in real time (DART), desorption atmospheric pressure chemical ionization (DAPCI), electrospray-assisted laser desertion/ionization (ELDI), matrix-assisted laser desorption electrospray ionization (MALDESI), extractive electrospray ionization (EESI), atmospheric solids analysis probe (ASAP), jet desorption ionization (JeDI) desorption sonic spray ionization (DeSSI), desorption atmospheric pressure photoionization (DAPPI), plasma-assisted desorption ionization (PADI), and dielectric barrier discharge ionization (DBDI).
DESI is a representative method for ambient mass spectrometry. It has been shown to be useful in providing a rapid and efficient means of desorbing, or ionizing, a variety of target compounds of interest under ambient conditions. For example, analytes such as pharmaceuticals, metabolites, drugs of abuse, explosives, chemical warfare agents, and biological tissues have all been studied with these ambient ionization methods.
However, DESI analysis has been restricted to solid samples. To analyze a fluid sample, the solution needed to be dried in air. Alternatively, the solution was passed through filter paper or a membrane (collectively “filters”), which captures the analyte, separating it from the solvent. This use of filters or drying sample in air was necessary because the high-velocity nebulizing gas used in direct analysis would blow away the liquid sample from the sample surface and result in a short-lived ion signal. However, these protocols increases the time, complexity, and/or cost for liquid sample analysis and may change the surrounding environment of analytes prior to analysis.
Ambient ionization sampling of solids, or liquid samples via filters, by DESI tended to have limited ability to desorb and ionize molecules greater than approximately 25 kDa in molecular weight. This was presumably due to the formation of molecular aggregates by intermolecular interactions within the closely-packed solid sample.
One potential method for direct analysis of liquid samples is extractive electrospray ionization (ESSI). ESSI requires two separate nebulizing sprayers: one to nebulize the sample solution and the other to nebulize the ionizing solvent solution. This method is dependent upon liquid-liquid extraction and the collision of microdroplets. Thus, several parameters must be controlled to extract the best possible ion signal for each target sample. This leads to greater complexity of both the method and device. Other existing methods for liquid sample analysis using mass spectrometry include electrospray-assisted laser desertion/ionization (ELDI) and field induced droplet ionization (FIDI). However, these methods require either laser or high electric fields to assist sample desorption thus increasing the protocol complexity.
Thus, there remains a need to easily analyze a range of target samples of interest using a simple device, including those of high molecular weights within a liquid matrix environment at ambient conditions. Therefore, it would be beneficial to develop an ambient ionization method, like DESI, for use with liquid samples. Such a method would be particularly useful in bioanalytical, forensic, pharmaceutical, and border security applications where direct and efficient analysis of liquids is needed.